DHX36-mediated G-quadruplexes unwinding is essential for oocyte and early embryo development in mice.

DHX36 plays a crucial role in regulating transcriptional and post-transcriptional processes through its interaction with G-quadruplexes (G4s). The mechanisms by which DHX36 regulates G4s vary across different cell types and physiological conditions. Oocyte-specific conditional knockout (CKO) mice were utilized to study the impact of DHX36 deficiency on female fertility.

Identification of G-quadruplex nucleic acid structures by high-throughput sequencing: A review.

G-quadruplexes (G4s) are non-canonical nucleic acid secondary structures formed by guanine-rich DNA or RNA sequences. These structures play pivotal roles in cellular processes, including DNA replication, transcription, RNA splicing, and protein translation. High-throughput sequencing has significantly advanced the study of G4s by enabling genome-wide mapping and detailed characterization.

PET Imaging of Solid Tumors with a G-Quadruplex-Targeting F-Labeled Peptide Probe.

Positron emission tomography (PET) is a common imaging technique and can provide accurate information about the size, shape, and location of tumors. Recent evidence has shown that G-quadruplex structures (G4s) are identified in human oncogenes, and these special structures are recognized as diagnostic cancer markers and drug targets for anticancer therapies. Although a number of techniques for in vivo imaging of G4s have been developed, achieving sufficient sensitivity and selectivity in vivo remains challenging.

Refraction/reflection reversal in two-dimensional acoustic metagratingsa).

Unlike acoustic metasurfaces that rely solely on phase gradients, acoustic metagratings (AMs) operate based on both phase gradients and grating diffraction, thus further extending the generalized Snell's law (GSL). In particular, AMs can achieve reversal of refraction and reflection based on the parity of the number of wave propagations inside the AMs. So far, discussions of this GSL extension have largely been applied to one-dimensional periodic AMs, while the designs of two-dimensional (2D) periodic AMs and their performance in three-dimensional (3D) space have been quite limited.

Icariside I enhances the effects of immunotherapy in gastrointestinal cancer via targeting TRPV4 and upregulating the cGAS-STING-IFN-I pathway.

Gastrointestinal cancer is among the most common cancers worldwide. Immune checkpoint inhibitor-based cancer immunotherapy has become an innovative approach in cancer treatment; however, its efficacy in gastrointestinal cancer is limited by the absence of infiltration of immune cells within the tumor microenvironment. Therefore, it is therefore urgent to develop a novel therapeutic drug to enhance immunotherapy.

Targeting hTERT Promoter G-Quadruplex DNA Structures with Small-Molecule Ligand to Downregulate hTERT Expression for Triple-Negative Breast Cancer Therapy.

Human telomerase reverse transcriptase (hTERT) may have noncanonical functions in transcriptional regulation and metabolic reprogramming in cancer cells, but it is a challenging target. We thus developed small-molecule ligands targeting hTERT promoter G-quadruplex DNA structures (hTERT G4) to downregulate hTERT expression. Ligand showed high affinity toward hTERT G4 ( = 1.

Lightweight and drift-free magnetically actuated millirobots via asymmetric laser-induced graphene.

Millirobots must have low cost, efficient locomotion, and the ability to track target trajectories precisely if they are to be widely deployed. With current materials and fabrication methods, achieving all of these features in one millirobot remains difficult. We develop a series of graphene-based helical millirobots by introducing asymmetric light pattern distortion to a laser-induced polymer-to-graphene conversion process; this distortion resulted in the spontaneous twisting and peeling off of graphene sheets from the polymer substrate.

Acoustic Metagrating Holograms.

Metasurface holograms represent a common category of metasurface devices that utilize in-plane phase gradients to shape wavefronts, forming holographic images through the application of the generalized Snell's law (GSL). While conventional metasurfaces focus solely on phase gradients, metagratings, which incorporate higher-order wave diffraction, further expand the GSL's generality. Recent advances in certain acoustic metagratings demonstrate an updated GSL extension capable of reversing anomalous transmission and reflection, whose reversal is characterized by the parity of the number of wave propagation trips through the metagrating.

Mitochondria-Selective Dicationic Small-Molecule Ligand Targeting G-Quadruplex Structures for Human Colorectal Cancer Therapy.

Mitochondria are important drug targets for anticancer and other disease therapies. Certain human mitochondrial DNA sequences capable of forming G-quadruplex structures (G4s) are emerging drug targets of small molecules. Despite some mitochondria-selective ligands being reported for drug delivery against cancers, the ligand design is mostly limited to the triphenylphosphonium scaffold.

Rotor-based image-guided therapy of glioblastoma.

Glioblastoma (GBM), deep in the brain, is more challenging to diagnose and treat than other tumors. Such challenges have blocked the development of high-impact therapeutic approaches that combine reliable diagnosis with targeted therapy. Herein, effective cyanine dyes (IRLy) with the near-infrared two region (NIR-II) adsorption and aggregation-induced emission (AIE) have been developed via an "extended conjugation & molecular rotor" strategy for multimodal imaging and phototherapy of deep orthotopic GBM.

Live Cell Imaging and Real-Time Monitoring of Nucleolus Morphology and Mitophagy with a Red Fluorescent and Photostable rRNA-Specific Probe in Human Cancer Cells.

rRNAs are prevalent in living organisms. They are produced in nucleolus and mitochondria and play essential cellular functions. In addition to the primary biofunction in protein synthesis, rRNAs have been recognized as the emerging signaling molecule and drug target for studies on nucleolus morphology, mitochondrial autophagy, and tumor cell malignancy.

Identification method of thyroid nodule ultrasonography based on self-supervised learning dual-branch attention learning framework.

Thyroid ultrasound is a widely used diagnostic technique for thyroid nodules in clinical practice. However, due to the characteristics of ultrasonic imaging, such as low image contrast, high noise levels, and heterogeneous features, detecting and identifying nodules remains challenging. In addition, high-quality labeled medical imaging datasets are rare, and thyroid ultrasound images are no exception, posing a significant challenge for machine learning applications in medical image analysis.

Intracranial infection and sepsis in infants caused by : A case report.

Background: () is a Gram-negative diplococcus that is common in the digestive tract. Infected patients generally experience symptoms such as fever and diarrhea. Mild cases are mostly self-healing gastroenteritis, and severe cases can cause fatal typhoid fever.

LDS-CNN: a deep learning framework for drug-target interactions prediction based on large-scale drug screening.

Background: Drug-target interaction (DTI) is a vital drug design strategy that plays a significant role in many processes of complex diseases and cellular events. In the face of challenges such as extensive protein data and experimental costs, it is suggested to apply bioinformatics approaches to exploit potential interactions to design new targeted medications. Different data and interaction types bring difficulties to study involving incompatible and heterology formats.

Bioinformatic assay reveal the potential mechanism of Guizhi-Shaoyao-Zhimu decoction against rheumatoid arthritis and mild-to-moderate COVID-19.

Background And Objective: Patients with rheumatoid arthritis (RA) are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than healthy population, but there is still no therapeutic strategy available for RA patients with corona virus disease 2019 (COVID-19). Guizhi-Shaoyao-Zhimu decoction (GSZD), Chinese ancient experience decoction, has a significant effect on the treatment of Rheumatism and gout. To prevent RA patients with mild-to-moderate COVID-19 from developing into severe COVID-19, this study explored the potential possibility and mechanism of GSZD in the treatment of this population.

A Cytoplasm-Specific Fluorescent Ligand for Selective Imaging of RNA G-Quadruplexes in Live Cancer Cells.

The development of site-specific, target-selective and biocompatible small molecule ligands as a fluorescent tool for real-time study of cellular functions of RNA G-quadruplexes (G4s), which are associated with human cancers, is of significance in cancer biology. We report a fluorescent ligand that is a cytoplasm-specific and RNA G4-selective fluorescent biosensor in live HeLa cells. The in vitro results show that the ligand is highly selective targeting RNA G4s including VEGF, NRAS, BCL2 and TERRA.

Aggregation-Induced emission photosensitizer with lysosomal response for photodynamic therapy against cancer.

Photosensitizers play a key role in bioimaging and photodynamic therapy (PDT) of cancer. However, conventional photosensitizers usually do not achieve the desired efficacy in PDT due to their poor photostability, targeting ability, and responsiveness. Herein, we designed a series of photosensitizers with aggregation-induced emission (AIE) effect using benzothiazole- triphenylamine (BZT-triphenylamine) as the parent nucleus.

All-in-one CoFeO@Tf nanoagent with GSH depletion and tumor-targeted ability for mutually enhanced chemodynamic/photothermal synergistic therapy.

In the complex and severe tumor microenvironment, the antitumor efficiency of nanomedicines is significantly limited by their low-efficacy monotherapy, non-tumor targeting, and systemic toxicity. Herein, to achieve tumor-targeted and enhanced chemodynamic/photothermal therapy (CDT/PTT), we fabricated an "all-in-one" biocompatible transferrin-loaded cobalt ferrate nanoparticle (CoFeO@Tf (CFOT)) with multiple functions by a simple solvothermal method and the following transferrin (Tf) functionalization. Upon exposure to 808 nm laser irradiation, CFOT, as a novel photothermal agent, exhibited outstanding phototherapeutic activity because of its excellent photothermal conversion efficiency ( = 46.

Computer-Aided Design of α-L-Rhamnosidase to Increase the Synthesis Efficiency of Icariside I.

Icariside I, the glycosylation product of icaritin, is a novel effective anti-cancer agent with immunological anti-tumor activity. However, very limited natural icariside I content hinders its direct extraction from plants. Therefore, we employed a computer-aided protein design strategy to improve the catalytic efficiency and substrate specificity of the α-L-rhamnosidase from DSM 13995, to provide a highly-efficient preparation method.

Novel quinoline-based derivatives as the PqsR inhibitor against Pseudomonas aeruginosa PAO1.

Aims: The emerging of drug resistant Pseudomonas aeruginosa is a critical challenge and renders an urgent action to discover innovative antimicrobial interventions. One of these interventions is to disrupt the pseudomonas quinolone signal (pqs) quorum sensing (QS) system, which governs multiple virulence traits and biofilm formation. This study aimed to investigate the QS inhibitory activity of a series of new PqsR inhibitors bearing a quinoline scaffold against Ps.

Design and synthesis of quinolinium-based derivatives targeting FtsZ for antibacterial evaluation and mechanistic study.

The discovery of small molecular inhibitors targeting essential and conserved bacterial drug targets such as FtsZ protein is a promising approach to fight against multi-drug resistant bacteria. In the present study, two new series of FtsZ inhibitors based on a 1-methylquinolinium scaffold were synthesized. The inhibitors possess a variety of substituent groups including the cyclic or linear amine skeleton at the 2- and 4-position of the quinolinium ring for structure-activity relationship study.

Rational design of small-molecules to recognize G-quadruplexes of c-MYC promoter and telomere and the evaluation of their in vivo antitumor activity against breast cancer.

DNA G4-structures from human c-MYC promoter and telomere are considered as important drug targets; however, the developing of small-molecule-based fluorescent binding ligands that are highly selective in targeting these G4-structures over other types of nucleic acids is challenging. We herein report a new approach of designing small molecules based on a non-selective thiazole orange scaffold to provide two-directional and multi-site interactions with flanking residues and loops of the G4-motif for better selectivity. The ligands are designed to establish multi-site interactions in the G4-binding pocket.

A mitochondria-targeted thiazoleorange-based photothermal agent for enhanced photothermal therapy for tumors.

Organic small molecules with near-infrared (NIR) absorption hold great promise as the phototheranostic agents for clinical translation by virtue of their inherent merits such as well-defined chemical structure, high purity and good reproducibility. Probes that happen to be based on cyanine dyes exhibit strong NIR-absorbing and efficient photothermal conversion, representing a new class of photothermal agents (PAs) for photothermal therapy (PTT), and taking into account the heat susceptibility of Mitochondria (Mito), we designed and prepared a mitochondria-targeted organic small molecule (Mito-BWQ) based on thiazole orange maternal unit that can effectively kill tumor cells through the hyperpyrexia generated in the lesions under exogenous laser irradiation. The Confocal laser scanning microscope was employed to determine the preferential targeting of Mito-BWQ to the mitochondria of MCF-7 cells and U87 cells.